In both men and women, narcotics exert major suppressive effects on sexual function. Chronic opiate addiction is associated with significant menstrual dysfunction-including frank amenorrhea-in women, or with diminished libido, impotence, and ejaculatory delay in men. Similar reproductive sequelae are recognized during long-term detoxification treatment with synthetic narcotics such as methadone. Conversely, treatment with potent opiate-receptor antagonists, such as naltrexone, is accompanied by demonstrable stimulation of gonadotropin secretion. At present, the precise pathophysiological mechanisms underlying these endocrine correlates of opiate action remain incompletely understood. In the present pilot studies in the human, we will investigate two discrete neuroendocrine mechanisms that modulate opiate action on reproductive hormone secretion. In particular, we will examine: 1) the role of excitatory noradrenergic mechanisms in mediating the stimulatory effects of treatment with opiate antagonists, and 2) the role of sex-steroid hormones in modulating inhibitory opiate mechanisms. For these purposes, we will apply precise quantitative methods that permit a more refined mathematical analysis of altered physiological patterns of pulsatile gonadotropin secretion in relation to opiate action. More exacting knowledge of the pathophysiological mechanisms that subserve endocrine effects of opiates in man will have significant implications for future therapy and research in the arena of narcotic addiction.